2,4-dihydroxybutyrate (also referred to as 2,4-DHB or DHB) is a highly useful chiral intermediate and is of considerable economic interest. DHB can be readily converted into α-hydroxy-γ-butyrolactone in aqueous media by adjusting to the appropriate pH. α-hydroxy-γ-butyrolactone is a prominent precursor for the production of the methionine substitute 2-hydroxy-4-(methylthio)-butyrate (HMTB), as described in U.S. Patent Application 2009/0318715, which has a large market in animal nutrition. DHB is also a promising precursor for biorenewable chemicals such as 3-hydroxypropanal, 3-hydroxypropionic acid, 3-propanediol, and malonic acid. DHB has been produced using complex metabolic engineering approaches as described in U.S. Patent Application Publication No. 2013/0273623, European Patent Application Publication Nos. 2841584 A2 and 2872640 A1. Such metabolic engineering approaches require expensive raw materials and complex reaction conditions. Other synthetic routes have used expensive raw materials such HMTB as described in U.S. Patent Application Publication No. 2013/0204016 A1. There remains a need for cost-effective methods to produce DHB.
The reaction of sugars in alkaline conditions have been studied since the nineteenth century. Sugars react with hydroxide in complicated pathways both in the presence of oxygen and in anaerobic conditions. For example, glucose or fructose react with oxygen gas in an alkaline water solution (see for example, as described in U.S. Pat. Nos. 4,125,559 and 5,831,078), where the 1-2 carbon bond is broken, yielding predominantly formic acid (from carbon 1) and arabinonic acid (from carbons 2-6). Also, large amounts of shorter carbon chain acids also are produced as described in Tapani Vuorinen, “Cleavage of the Intermediate Hydroperoxides in the Oxidation of D-Glucose and D-Fructose with Oxygen,” Carbohydrate Research, 141 (1985): 319-332. Anaerobic reactions of sugars in alkaline conditions are generally termed degradations and result in complex mixtures of reaction products that are difficult to analyze but that include small amounts of DHB, as described in Byung Yun Yang and Rex Montgomery, “Alkaline Degradation of Glucose: Effect of Initial Concentration of Reactants,” Carbohydrate Research 280 (1996): 27-45, and J. F. Harris, “Alkaline Decomposition of D-Xylose-1-14C, D-Glucose-1-14C, and D-Glucose-6-14C,” Carbohydrate Research 23 (July 1972): 207-215. Moreover, compounds such as Class I Caramel Color are created by reacting glucose with hydroxide in anaerobic conditions. Under milder alkaline conditions glucose is known to merely isomerize into fructose, as described in U.S. Pat. No. 3,256,270. Because oxygen is sparingly soluble in water, often degradations occur when open to the atmosphere.
There remains a need in the art for cost effective methods for the production of DHB from four carbon sugars such as erythrose. Erythrose itself is a rare four carbon sugar that has recently been produced on a large scale via electrochemical decarboxylation as described in U.S. Patent Application Publication No. 2007/0181437. The present disclosure provides a method of converting four-carbon sugars, to four-carbon DHB by reacting the sugars in an alkaline solution.